The candidate is a dual-trained pediatric and adult rheumatologist whose career goal is to become an independent clinical investigator committed to identifying the role of inflammation and immune dysregulation in the process of accelerated atherosclerosis in systemic lupus erythematosus (SLE). Her dual training provides a unique opportunity for her to identify, treat, and prevent this complication in SLE patients of all ages. As more SLE patients are surviving complications of their underlying disease they are experiencing significant morbidity and mortality from cardiovascular disease (CVD). It is likely that the etiology of CVD in SLE patients is multifactorial, including traditional risk factors as well mediated by as immune and inflammatory mechanisms. A case-control study of 228 SLE subjects and 114 age, sex, and race-matched controls, with longitudinal follow-up (up to 3.5 years), is proposed to quantify differences in subclinical atherosclerosis and underlying CVD risk factors in SLE patients compared to controls. Subclinical atherosclerosis will be assessed using complementary non-invasive measures, including carotid ultrasound (e.g. measuring intimal medial thickness) and multi-slice computed tomography (e.g. for coronary artery calcification). Risk factor assessment will include traditional CVD risk factors as well as novel risk factors, including markers of immune dysregulation such as soluble CD154. CVD events will be identified with annual event ascertainment. Differences between SLE and controls will be described and quantified. In SLE, the extent to which traditional, novel and SLE-disease specific risk factors are associated with indices of subclinical atherosclerosis will be quantified. Potential racial differences in disease expression will be explored. This project will provide an excellent "hands-on" opportunity to develop a unique cohort for ongoing follow-up while also generating new data that characterize CVD risk factors and quantify any excessive risk of subclinical and clinical atherosclerosis in SLE. Studying the role of novel indices of immune dysregulation in subclinical atherosclerosis may provide new insights into CVD pathogenesis. This research plan will be complemented with a 5-year training program with a team of experienced faculty mentors and exceptional institutional support. Training activities include advanced coursework leading to a Master of Science in Clinical Research, independent study, and mentored-patient-based research. These activities will provide an essential training opportunity to foster the candidate's career development as a clinical researcher with a commitment to making significant contributions to the field of autoimmunity and its involvement in CVD. Atherosclerosis prevention and interventional strategies will depend on the identification of risk factors and surrogate markers, as well as understanding the underlying pathogenesis of the disease. SLE, an inflammatory and immune-dysregulated disease, may provide an ideal model of CVD.